CA2629311C - Glucagon receptor antagonists, preparation and therapeutic uses - Google Patents

Glucagon receptor antagonists, preparation and therapeutic uses Download PDF

Info

Publication number: CA2629311C
Authority: CA; Canada
Prior art keywords: dimethyl; thiophene; biphenyl; carboxylic acid; amide
Prior art date: 2005-11-23
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2629311A

Other languages

English (en)

French (fr)

Other versions

CA2629311A1 (en

Inventor

Mark Donald Chappell

Scott Eugene Conner

Philip Arthur Hipskind

Allie Edward Tripp

Guoxin Zhu

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Eli Lilly and Co

Original Assignee

Eli Lilly and Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2005-11-23

Filing date

2006-11-21

Publication date

2014-05-06

2006-11-21 Application filed by Eli Lilly and Co filed Critical Eli Lilly and Co

2007-10-25 Publication of CA2629311A1 publication Critical patent/CA2629311A1/en

2014-05-06 Application granted granted Critical

2014-05-06 Publication of CA2629311C publication Critical patent/CA2629311C/en

Status Expired - Fee Related legal-status Critical Current

2026-11-21 Anticipated expiration legal-status Critical

Links

229940122904 Glucagon receptor antagonist Drugs 0.000 title abstract description 9
238000002360 preparation method Methods 0.000 title description 38
230000001225 therapeutic effect Effects 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 153
206010012601 diabetes mellitus Diseases 0.000 claims abstract description 30
150000003839 salts Chemical class 0.000 claims abstract description 27
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
229910052736 halogen Inorganic materials 0.000 claims description 95
150000002367 halogens Chemical class 0.000 claims description 66
-1 3,3-dimethylbutyl Chemical group 0.000 claims description 51
ZHCLIFKUVIFYBY-UHFFFAOYSA-N 2h-tetrazol-5-ylmethanamine Chemical compound NCC1=NN=NN1 ZHCLIFKUVIFYBY-UHFFFAOYSA-N 0.000 claims description 31
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
238000011282 treatment Methods 0.000 claims description 27
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
239000003814 drug Substances 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 11
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
125000003342 alkenyl group Chemical group 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 5
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000000439 4-methylpentoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
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ULVIXJPSVNNLQE-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanyl-3-methylbutyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C=C(C(=O)NCC=2NN=NN=2)SC=1C(CC(C)C)SC(C=C1C)=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 ULVIXJPSVNNLQE-UHFFFAOYSA-N 0.000 claims 2
VQAZHBAPCPZVGY-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanylpentyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C=C(C(=O)NCC=2NN=NN=2)SC=1C(CCCC)SC(C=C1C)=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 VQAZHBAPCPZVGY-UHFFFAOYSA-N 0.000 claims 2
FHSPIZOLUZGKDA-UHFFFAOYSA-N 5-[1-[4-(4-tert-butylphenyl)-3,5-dimethylphenyl]sulfanyl-2,2-dimethylpropyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(C)(C)C)C(C)=CC=1SC(C(C)(C)C)C(S1)=CC=C1C(=O)NCC=1N=NNN=1 FHSPIZOLUZGKDA-UHFFFAOYSA-N 0.000 claims 2
OHJQJUXJVGUOEP-UHFFFAOYSA-N 5-[1-[4-(4-tert-butylphenyl)-3,5-dimethylphenyl]sulfanylpropyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C=C(C(=O)NCC2=NNN=N2)SC=1C(CC)SC(C=C1C)=CC(C)=C1C1=CC=C(C(C)(C)C)C=C1 OHJQJUXJVGUOEP-UHFFFAOYSA-N 0.000 claims 2
NYYGWCMQGHADAH-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanyl-2,2-dimethylpropyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)C(C)=CC=1SC(C(C)(C)C)C(S1)=CC=C1C(=O)NCC1=NN=NN1 NYYGWCMQGHADAH-UHFFFAOYSA-N 0.000 claims 1
BZZPIRSETRDIPE-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanyl-2,2-dimethylpropyl]thiophene-2-carboxylic acid Chemical compound C=1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)C(C)=CC=1SC(C(C)(C)C)C1=CC=C(C(O)=O)S1 BZZPIRSETRDIPE-UHFFFAOYSA-N 0.000 claims 1
CUGPERPOARNZLC-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanyl-2-methylpropyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C=C(C(=O)NCC=2NN=NN=2)SC=1C(C(C)C)SC(C=C1C)=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 CUGPERPOARNZLC-UHFFFAOYSA-N 0.000 claims 1
JCEKALXHEUXGLX-UHFFFAOYSA-N 5-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]phenyl]sulfanylbutyl]-n-(2h-tetrazol-5-ylmethyl)thiophene-2-carboxamide Chemical compound C=1C=C(C(=O)NCC=2NN=NN=2)SC=1C(CCC)SC(C=C1C)=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 JCEKALXHEUXGLX-UHFFFAOYSA-N 0.000 claims 1
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229960004666 glucagon Drugs 0.000 abstract description 63
102000051325 Glucagon Human genes 0.000 abstract description 61
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives

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CA2629311A 2005-11-23 2006-11-21 Glucagon receptor antagonists, preparation and therapeutic uses Expired - Fee Related CA2629311C (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US73969205P	2005-11-23	2005-11-23
US60/739,692		2005-11-23
PCT/US2006/061132 WO2007120284A2 (en)	2005-11-23	2006-11-21	Glucagon receptor antagonists, preparation and therapeutic uses

Publications (2)

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CA2629311A1 CA2629311A1 (en)	2007-10-25
CA2629311C true CA2629311C (en)	2014-05-06

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CA2629311A Expired - Fee Related CA2629311C (en)	2005-11-23	2006-11-21	Glucagon receptor antagonists, preparation and therapeutic uses

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US (1)	US7807702B2 (de)
EP (1)	EP1957484B1 (de)
JP (1)	JP5140599B2 (de)
CN (1)	CN101312963B (de)
AT (1)	ATE459619T1 (de)
AU (1)	AU2006342059B2 (de)
BR (1)	BRPI0618745A2 (de)
CA (1)	CA2629311C (de)
CY (1)	CY1110922T1 (de)
DE (1)	DE602006012725D1 (de)
DK (1)	DK1957484T3 (de)
ES (1)	ES2339599T3 (de)
PL (1)	PL1957484T3 (de)
PT (1)	PT1957484E (de)
SI (1)	SI1957484T1 (de)
WO (1)	WO2007120284A2 (de)

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WO2008098244A1 (en)	2007-02-09	2008-08-14	Metabasis Therapeutics, Inc.	Novel antagonists of the glucagon receptor
EP2025674A1 (de)	2007-08-15	2009-02-18	sanofi-aventis	Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel
CN104803891B (zh)	2008-08-13	2017-10-20	症变治疗公司	胰高血糖素拮抗剂
WO2011107494A1 (de)	2010-03-03	2011-09-09	Sanofi	Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung
US8933024B2 (en)	2010-06-18	2015-01-13	Sanofi	Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
US8530413B2 (en)	2010-06-21	2013-09-10	Sanofi	Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments
TW201215388A (en)	2010-07-05	2012-04-16	Sanofi Sa	(2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments
TW201221505A (en)	2010-07-05	2012-06-01	Sanofi Sa	Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
TW201215387A (en)	2010-07-05	2012-04-16	Sanofi Aventis	Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament
MX2013006768A (es)	2010-12-23	2013-07-22	Pfizer	Moduladores de receptor de glucagon.
ES2597972T3 (es)	2011-02-08	2017-01-24	Pfizer Inc	Modulador del receptor de glucagón
WO2012120056A1 (de)	2011-03-08	2012-09-13	Sanofi	Tetrasubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2683704B1 (de)	2011-03-08	2014-12-17	Sanofi	Verzweigte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
US8710050B2 (en)	2011-03-08	2014-04-29	Sanofi	Di and tri- substituted oxathiazine derivatives, method for the production, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120054A1 (de)	2011-03-08	2012-09-13	Sanofi	Di- und trisubstituierte oxathiazinderivate, verfahren zu deren herstellung, ihre verwendung als medikament sowie sie enthaltendes arzneimittel und deren verwendung
EP2766349B1 (de)	2011-03-08	2016-06-01	Sanofi	Mit carbozyklen oder heterozyklen substituierte oxathiazinderivate, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung
RU2013157388A (ru)	2011-07-22	2015-08-27	Пфайзер Инк.	Хинолинильные модуляторы глюкагонового рецептора
WO2013037390A1 (en)	2011-09-12	2013-03-21	Sanofi	6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2013045413A1 (en)	2011-09-27	2013-04-04	Sanofi	6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
EP3065736B1 (de)	2013-11-04	2018-11-14	Merck Sharp & Dohme Corp.	Glucagon-rezeptor-antagonist-verbindungen, zusammensetzungen daraus und verfahren zur verwendung
JP2017519000A (ja)	2014-06-12	2017-07-13	リガンド・ファーマシューティカルズ・インコーポレイテッド	グルカゴンアンタゴニスト
JP2021513564A (ja)	2018-02-13	2021-05-27	リガンド・ファーマシューティカルズ・インコーポレイテッド	グルカゴン受容体拮抗薬

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WO2002000612A1 (en) *	2000-06-23	2002-01-03	Novo Nordisk A/S	Glucagon antagonists/inverse agonists
EP1463715A1 (de)	2001-12-03	2004-10-06	Novo Nordisk A/S	Neue glucagonantagonisten
JP2006500325A (ja)	2002-06-27	2006-01-05	ノボ　ノルディスク　アクティーゼルスカブ	新規なグルカゴンアンタゴニスト
AU2003291959A1 (en)	2002-12-20	2004-07-14	Novo Nordisk A/S	Novel glucagon antagonists
CN101146762A (zh)	2005-03-21	2008-03-19	默克公司	取代的芳基和杂芳基衍生物

2006
- 2006-11-21 JP JP2008542509A patent/JP5140599B2/ja not_active Expired - Fee Related
- 2006-11-21 CA CA2629311A patent/CA2629311C/en not_active Expired - Fee Related
- 2006-11-21 DE DE602006012725T patent/DE602006012725D1/de active Active
- 2006-11-21 EP EP06850798A patent/EP1957484B1/de not_active Not-in-force
- 2006-11-21 SI SI200630650T patent/SI1957484T1/sl unknown
- 2006-11-21 US US12/094,406 patent/US7807702B2/en not_active Expired - Fee Related
- 2006-11-21 DK DK06850798.7T patent/DK1957484T3/da active
- 2006-11-21 WO PCT/US2006/061132 patent/WO2007120284A2/en not_active Ceased
- 2006-11-21 AT AT06850798T patent/ATE459619T1/de active
- 2006-11-21 AU AU2006342059A patent/AU2006342059B2/en not_active Ceased
- 2006-11-21 CN CN2006800438950A patent/CN101312963B/zh not_active Expired - Fee Related
- 2006-11-21 BR BRPI0618745-5A patent/BRPI0618745A2/pt not_active IP Right Cessation
- 2006-11-21 PT PT06850798T patent/PT1957484E/pt unknown
- 2006-11-21 ES ES06850798T patent/ES2339599T3/es active Active
- 2006-11-21 PL PL06850798T patent/PL1957484T3/pl unknown
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ES2339599T3 (es)	2010-05-21
CN101312963A (zh)	2008-11-26
JP2009519903A (ja)	2009-05-21
SI1957484T1 (sl)	2010-07-30
JP5140599B2 (ja)	2013-02-06
PL1957484T3 (pl)	2010-07-30
WO2007120284A2 (en)	2007-10-25
EP1957484B1 (de)	2010-03-03
ATE459619T1 (de)	2010-03-15
US20080300289A1 (en)	2008-12-04
BRPI0618745A2 (pt)	2011-09-13
CN101312963B (zh)	2012-03-14
PT1957484E (pt)	2010-03-29
DK1957484T3 (da)	2010-05-10
EP1957484A2 (de)	2008-08-20
WO2007120284A3 (en)	2007-12-27
AU2006342059A1 (en)	2007-10-25
AU2006342059B2 (en)	2012-05-10
DE602006012725D1 (de)	2010-04-15
CY1110922T1 (el)	2015-06-10
US7807702B2 (en)	2010-10-05
CA2629311A1 (en)	2007-10-25

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2010-11-08	EEER	Examination request
2017-01-02	MKLA	Lapsed	Effective date: 20161121

Publication	Publication Date	Title
US7696248B2 (en)	2010-04-13	Glucagon receptor antagonists, preparation and therapeutic uses
EP1957484B1 (de)	2010-03-03	Glucagonrezeptorantagonisten, deren herstellung und therapeutische verwendung
CA2629172C (en)	2014-05-06	Glucagon receptor antagonists, preparation and therapeutic uses
EP1951658B1 (de)	2012-09-26	Glucagonrezeptorantagonisten, deren herstellung und therapeutische verwendung
CA2629321C (en)	2013-08-06	Glucagon receptor antagonists, preparation and therapeutic uses
EP1951659B1 (de)	2010-07-14	Glucagonrezeptorantagonisten, deren herstellung und therapeutische verwendung
MX2008006699A (en)	2008-09-02	Glucagon receptor antagonists, preparation and therapeutic uses